The Vitamin A Laboratory (VitAL) research program: fundamental insight into vitamin A metabolism

维生素 A 实验室 (VitAL) 研究计划：维生素 A 代谢的基本见解

• 批准号: RGPIN-2017-04710
• 负责人: Clugston, Robin
• 金额: $ 1.89万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647854
• 关键词: Vitamin; Laboratory; VitAL; research; program

Vitamin A is an essential micronutrient, required to maintain good health in humans and other animals. Since its discovery over 100 years ago, much has been learned about vitamin A biology; however, there remain fundamental gaps in our knowledge concerning its metabolism and function. Vitamin A is required to fulfill some of the body's most basic functions, with critical roles in vision, immunity and reproduction. The necessity of adequate vitamin A intake is highlighted in the developing world, where its deficiency is associated with high infant mortality and childhood blindness. Although vitamin A deficiency is not a major issue in Canada, the contribution of impaired vitamin A function to certain cancers, birth defects and metabolic diseases, underscores its importance. With this in mind, the overall goal of the Vitamin A Laboratory's (VitAL) research program is to improve our understanding of basic vitamin A biology.***Our research program focuses on providing a better understanding of how the body processes and uses vitamin A. We are particularly interested in the liver, because this organ serves as the body's vitamin A warehouse and distribution center. Specifically, the liver contains the largest store of vitamin A in the body, and secretes it at a steady rate to supply the rest of the body. Based on our preliminary data, we have identified a previously unrecognized role for the fatty acid transporter CD36 in vitamin A metabolism. The proposed work involves studying CD36 at the whole organism, cellular, and molecular level, and tests the central hypothesis that CD36 is a novel contributor to hepatic vitamin A metabolism. Methodologically, this work will involve studying Cd36 knockout mice, inhibiting CD36 function in isolated liver cells, and assaying vitamin A-CD36 interactions at the molecular level.***Improving our basic understanding of vitamin A metabolism is fundamentally important. The novel work described in this proposal will lead to the identification of CD36 as a hitherto unrecognized contributor to vitamin A biology, representing an important discovery in the field. This new knowledge will be relevant to those interested in the life sciences, including nutritionists, physiologists and biochemists. In the Canadian context, this country has a global reputation in providing vitamin A supplements to the developing world. Dubbed “Canada's vitamin A success story”, vitamin A supplements provided through the Micronutrient Initiative, and funded by the Canadian government, have helped save millions of children's lives. By establishing an internationally recognized program of excellence into studying vitamin A biology, our work will further bolster Canada's reputation and impact, providing a basic scientific program to complement the established excellence in the country's global health efforts.

维生素A是一种必需的微量营养素，是维持人类和其他动物健康所必需的。自从100多年前发现维生素A以来，人们对维生素A的生物学已经有了很多了解;然而，我们对维生素A的代谢和功能的了解仍然存在根本性的空白。维生素A是实现身体一些最基本功能所必需的，在视力、免疫力和生殖方面起着关键作用。发展中国家强调必须摄入足够的维生素A，缺乏维生素A与婴儿死亡率和儿童失明率高有关。虽然维生素A缺乏症在加拿大不是一个主要问题，但维生素A功能受损对某些癌症、出生缺陷和代谢疾病的影响突出了它的重要性。考虑到这一点，维生素A实验室（VitAL）研究计划的总体目标是提高我们对基本维生素A生物学的理解。我们的研究计划侧重于更好地了解身体如何处理和使用维生素A。我们对肝脏特别感兴趣，因为这个器官是人体维生素A的仓库和配送中心。 具体来说，肝脏含有体内最大的维生素A储存，并以稳定的速度分泌维生素A以供应身体的其他部分。基于我们的初步数据，我们已经确定了一个以前未被认识的作用，脂肪酸转运蛋白CD 36在维生素A代谢。拟议的工作涉及在整个生物体，细胞和分子水平上研究CD 36，并测试中心假设，即CD 36是肝脏维生素A代谢的新贡献者。在方法上，这项工作将涉及研究Cd 36敲除小鼠，抑制分离肝细胞中的CD 36功能，并在分子水平上测定维生素A-CD 36相互作用。提高我们对维生素A代谢的基本认识至关重要。本提案中描述的新工作将导致鉴定CD 36作为迄今未被认识到的维生素A生物学贡献者，代表该领域的重要发现。这些新知识将与那些对生命科学感兴趣的人相关，包括营养学家、生理学家和生物化学家。就加拿大而言，该国在向发展中国家提供维生素A补充剂方面享有全球声誉。由加拿大政府资助、通过微量营养素计划提供的维生素A补充剂被称为“加拿大维生素A成功故事”，帮助挽救了数百万儿童的生命。通过建立一个国际公认的卓越计划来研究维生素A生物学，我们的工作将进一步提高加拿大的声誉和影响力，提供一个基本的科学计划，以补充该国在全球健康方面的卓越成就。